After Mr. Epp and the Calculations ended, Mark Arm and Steve Turner (who had become close friends) joined the band Limp Richerds for a few weeks. Afterward, Arm and Turner took on future Pearl Jam members Jeff Ament and Stone Gossard, as well as Alex Vincent, to form the band Green River. Green River released two EPs and a full length album before disbanding. Steve Turner left the band to finish college, and Arm was forced to find a new band again. After Turner returned from schooling, they resumed their Green River side project, The Thrown Ups.

Arm and Turner took on drummer Dan Peters, and bassist Matt Lukin, formerly of Melvins. The new band renamed themselves Mudhoney. In 1988, Sub Pop released Mudhoney's first single, "Touch Me I'm Sick". After extensive touring and an EP album, Mudhoney released their eponymous full length debut in 1989. Their next album, Every Good Boy Deserves Fudge came out soon after, just before the explosion of grunge spearheaded by Nirvana's seminal Nevermind. At the time, Sub Pop, their record label, was "on the verge of bankruptcy, having trouble paying its flagship band, severely delaying the release of the album to July 1991."[3] In 1992, they signed to a major record label, Reprise and released Piece of Cake. The album did not sell well, due to a combination of the band's uncompromising sound and an oversaturation of the genre; according to Stephen Turner, the album references "how easily things had come to them...the songs were kinda half-baked... and Mark wasn't at his best."[3]

Although they never achieved the fame of some of their contemporaries, Arm and Mudhoney have made significant contributions to grunge music. Mudhoney is one of the few grunge bands that continue to release albums; in 2002 they released Since We've Become Translucent, The Lucky Ones in May 2008 on the Sub Pop label, and Vanishing Point, their latest release, in April 2013 on the Sub Pop label again.

When grunge exploded in the early '90s, Arm wrote a comedic nonfiction essay about smoking pot and going to the Clinton White House with Pearl Jam.

In 2008, he told the Washington Post's Express, "I don't smoke pot all that much. I did get stoned last night, though [laughs] – after the show. I'm not opposed smoking pot or to people smoking pot. Every now and again I smoke a joint, but I don't get stoned and come up with creative ideas. I usually get paralyzed on the couch."

According to a recent article in magazine, MOJO, Mark Arm started using heroin in 1987 and by the summer of 1989, "...it had all caught up with me.". Apparently, the band had little patience for his addiction, so he would "use heroin when Mudhoney were off the road, then stop as they prepared to leave. 'So I was real used to quitting,' Arm says. 'You go through these flu-like symptoms for a couple of days, then you think about it for months.'" Arm hit his nadir on New Year's Eve 1992 when he overdosed for the fourth time. He stopped using heroin in 1993 upon becoming involved with Emily Rieman, now his wife.